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The primary cause of mortality in colorectal cancer (CRC) patients is tumor metastasis. The epithelial-mesenchymal transition (EMT) stands out as a crucial factor promoting the metastasis of CRC. Previous findings suggest a potential inhibitory effect of docosahexaenoic acid (DHA) on CRC metastasis, but the precise mechanism remains unknown, this study aims to explore this issue. We assessed metastasis and recurrence, all-cause mortality, and cancer-related mortality rates according to DHA intake in independent CRC cohorts (n = 367) by survival analysis. The ability of DHA to block CRC cell migration and invasion was tested using transwell and wound-healing assays. The regulation of EMT marker genes in CRC by DHA was detected by quantitative real-time PCR (qPCR) and immunoblotting, and the effect of DHA on the TGF-ß1/Smad signaling pathway was further investigated. These cellular findings were validated using a subcutaneous CRC mouse model. Survival analyses showed that lower DHA intake was associated with a higher risk of CRC metastasis and a poorer prognosis. In vitro experiments showed that DHA inhibits the TGF-ß1/Smad signaling pathway and regulates downstream transcription factors, thereby reversing the EMT and inhibiting invasion and migration. In the mouse model, dietary DHA supplementation effectively increased blood DHA concentrations and inhibited CRC metastasis. Our study demonstrated that DHA inhibits CRC invasion and metastasis by inhibiting the TGF-ß1/Smad signaling pathway. Increased intake of DHA among CRC patients may provide additional benefits to the prognosis of colorectal cancer.
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BACKGROUND: Non-suicidal self-injury (NSSI) is a risk factor for suicide. This study aimed to investigate the prevalence of NSSI and professional psychological help-seeking status and influencing factors among left-behind children (LBC) in China. METHODS: We implemented a population-based cross-sectional study in participants aged 10-18 years. Sociodemographic characteristics, NSSI, help-seeking status and coping style were measured by self-reported questionnaires. A total of 16,866 valid questionnaires were collected, including 6096 LBC. Binary logistic regression models were used to analyze the factors influencing NSSI and professional psychological help-seeking. RESULTS: The incidence of NSSI among LBC was 4.6%, significantly higher than that of non-left-behind children (NLBC). This incidence was higher among girls. Moreover, 53.9% of LBC with NSSI did not receive any treatment and only 22.0% sought professional psychological help. LBC often adopt emotion-oriented coping styles, specifically, those with NSSI. LBC with NSSI who seek professional help tend to adopt problem-oriented coping styles. Logistic regression analysis revealed that girls, learning stage, single-parent, remarried families, patience, and emotional venting were risk factors for NSSI in LBC, while problem-solving and social support seeking were protective factors. Moreover, problem-solving was also a predictor for seeking professional psychological help, patience will prevent it. LIMITATIONS: This was an online survey. CONCLUSIONS: The prevalence of NSSI in LBC is high. Gender, grade, family structure, and coping style affect the occurrence of NSSI among LBC. Only a few LBC with NSSI seek professional psychological help, while the coping style will affect the help-seeking behavior.
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População do Leste Asiático , Comportamento Autodestrutivo , Criança , Feminino , Humanos , China/epidemiologia , Estudos Transversais , Emoções , Prevalência , Fatores de Risco , Comportamento Autodestrutivo/epidemiologia , Comportamento Autodestrutivo/psicologia , Inquéritos e Questionários , Masculino , AdolescenteRESUMO
The perfluorooctane sulfonate alternative, F-53B, induces multiple physiological defects but whether it can disrupt eye development is unknown. We exposed zebrafish to F-53B at four different concentrations (0, 0.15, 1.5, and 15 µg/L) for 120 h post-fertilization (hpf). Locomotor behavior, neurotransmitters content, histopathological alterations, morphological changes, cell apoptosis, and retinoic acid signaling were studied. Histology and morphological analyses showed that F-53B induced pathological changes in lens and retina of larvae and eye size were significantly reduced as compared to control. Acridine orange (AO) staining revealed a dose-dependent increase in early apoptosis, accompanied by upregulation of p53, casp-9 and casp-3 genes. Genes related to retinoic acid signaling (aldh1a2), lens developmental (cryaa, crybb, crygn, and mipa) and retinal development (pax6, rx1, gant1, rho, opn1sw and opn1lw) were significantly downregulated. In addition, behavioral responses (swimming speed) were significantly increased, while no significant changes in the neurotransmitters (dopamine and acetylcholine) level were observed. Therefore, in this study we observed that exposure to F-53B inflicted histological and morphological changes in zebrafish larvae eye, induced visual motor dysfunctions, perturbed retinoid signaling and retinal development and ultimately triggering apoptosis.
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Poluentes Químicos da Água , Peixe-Zebra , Acetilcolina , Laranja de Acridina/análise , Alcanossulfonatos/análise , Animais , Dopamina , Larva , Retinoides , Tretinoína , Proteína Supressora de Tumor p53 , Poluentes Químicos da Água/análise , Poluentes Químicos da Água/toxicidadeRESUMO
BACKGROUND: Studies on the obesogenic effect of air pollution on children have been mixed and sparse. Moreover, due to insufficient air monitoring, few studies have investigated the role of more tiny but unregulated particles (ambient particles with a diameter of 0.1 µm or less, ultrafine particles). OBJECTIVE: We sought to explore the associations between long-term exposure to ambient ultrafine particles (UFPs) and childhood obesity in Chinese children. METHODS: In this cross-sectional study, we randomly recruited 47,990 children, aged 6-18 years, from seven cities in Northeastern China between 2012 and 2013. Child age- and sex-specific z-scores for body mass index (BMI Z-score) and weight status were generated using the World Health Organization growth reference. Four-year average concentrations of UFPs and airborne particulates of diameter ≤ 1 µm (PM1), ≤2.5 µm (PM2.5), and ≤10 µm (PM10) were estimated at home, using neural network simulated WRF-Chem model and spatiotemporal model, respectively. Confounder-adjusted generalized linear mixed models examined the associations between air pollution and BMI Z-score and the prevalence of childhood obesity. RESULT: We found that UFPs exposure was associated with greater childhood BMI Z-score and a higher likelihood of obesity. Compared with the lowest quartile, higher quartiles of UFPs were associated with greater odds for obesity prevalence in children (i.e., the adjusted OR was 1.25; 95 % CI, 1.12-1.39; 1.43; 95 % CI, 1.27-1.61; and 1.41; 95 % CI, 1.25-1.58 for the second, third, and fourth quartile, respectively). Similar associations were observed for PM1, PM2.5, and PM10, and were greater in boys and children living close to roadways. CONCLUSIONS: Long-term UFPs exposure was associated with a greater likelihood of childhood obesity, and stronger associations on BMI Z-score were observed in boys and children living close to roadways. This study indicates that more attention should be paid to the health effects of UFPs, and routinely monitoring of UFPs should be considered.
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Poluentes Atmosféricos , Poluição do Ar , Obesidade Infantil , Poluentes Atmosféricos/análise , Poluição do Ar/análise , Criança , China/epidemiologia , Cidades , Estudos Transversais , Exposição Ambiental/análise , Feminino , Humanos , Masculino , Material Particulado/análise , Obesidade Infantil/epidemiologiaRESUMO
Experimental evidence has shown that per- and polyfluoroalkyl substances (PFAS) alternatives and mixtures may exert hepatotoxic effects in animals. However, epidemiological evidence is limited. This research aimed to explore associations of PFAS and the alternatives with liver function in a general adult population. The study participants consisted of 1,303 adults from a community-based cross-sectional investigation in Guangzhou, China, from November 2018 to August 2019. We selected 13 PFAS with detection rates > 85% in serum samples and focused on perfluorooctane-sulfonic acid (PFOS), perfluorooctanoic acid (PFOA) and their alternatives [6:2 chlorinated polyfluorinated ether sulfonate (6:2 Cl-PFESA), 8:2 Cl-PFESA, and perfluorohexanoic acid (PFHxA)] as predictors of outcome. Six liver function biomarkers (ALB, ALT, AST, GGT, ALP, and DBIL) were chosen as outcomes. We applied regression models with restricted cubic spline function to explore correlations between single PFAS and liver function and inspected the combined effect of PFAS mixtures on liver by applying Bayesian kernel machine regression (BKMR). We discovered positive associations among PFAS and liver function biomarkers except for ALP. For example, compared with the 25th percentile of PFAS concentration, the level of ALT increased by 12.36% (95% CI: 7.91%, 16.98%) for ln-6:2 Cl-PFESA, 5.59% (95% CI: 2.35%, 8.92%) for ln-8:2 Cl-PFESA, 3.56% (95% CI: -0.39%, 7.68%) for ln-PFHxA, 13.91% (95% CI: 8.93%, 19.13%) for ln-PFOA, and 14.25% (95% CI: 9.91%, 18.77%) for ln-PFOS at their 75th percentile. In addition, higher exposed serum PFAS was found to be correlated with greater odds of abnormal liver function. Analysis from BKMR models also showed an adverse association between PFAS mixtures and liver function. The combined effect of the PFAS mixture appeared to be non-interactive, in which PFOS was the main contributor to the overall effect. Our findings provide evidence of associations between PFAS alternatives, PFAS mixtures, and liver function in the general adult population.
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Ácidos Alcanossulfônicos , Poluentes Ambientais , Fluorocarbonos , Ácidos Alcanossulfônicos/análise , Ácidos Alcanossulfônicos/toxicidade , Teorema de Bayes , China/epidemiologia , Estudos Transversais , Poluentes Ambientais/análise , Poluentes Ambientais/toxicidade , Fluorocarbonos/análise , Fluorocarbonos/toxicidade , Humanos , Fígado/químicaRESUMO
It has been reported that exposure to perfluorooctane sulfonates (PFOS) causes behavioral abnormalities in zebrafish larvae, but the possible mechanisms underlying these changes remain unexplored. In this study, zebrafish embryos (2 h postfertilization, 2-hpf) were exposed to PFOS at different concentrations (0, 0.032, 0.32 and 3.2 mg/L) for 120 h. Developmental endpoints and the locomotion behavior of larvae were evaluated. Reactive oxygen species (ROS) levels, dopamine contents, several genes and proteins related to neurodevelopment and dopamine signaling were examined. Our results indicate that increased ROS levels in the zebrafish larvae heads may be causally associated with neurodevelopment damage. Meanwhile, brain-derived neurotrophic factor (BDNF) and alpha1-Tubulin (α1-Tubulin) protein contents were significantly increased, which may be a compensatory mechanism for the impaired central nervous system. PFOS-induced locomotor hyperactivity was observed in the first light phase and dark phase at the 0.32 and 3.2 mg/L of PFOS. Upregulation of dopamine-related genes tyrosine hydroxylase (th) and dopamine transporter (dat) associated with increased dopamine contents in the 3.2 mg/L of PFOS. In addition, protein expression of TH and DAT were noted at the 0.32 and 3.2 mg/L of PFOS concentrations. Our results suggested that PFOS induces neurobehavioral changes in zebrafish larvae, possibly by perturbing a dopamine signaling pathway. In addition, PFOS induced development damage, such as increased malformation rate and shorter body length.
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Ácidos Alcanossulfônicos , Fluorocarbonos , Poluentes Químicos da Água , Ácidos Alcanossulfônicos/metabolismo , Ácidos Alcanossulfônicos/toxicidade , Animais , Dopamina/metabolismo , Embrião não Mamífero/metabolismo , Fluorocarbonos/metabolismo , Fluorocarbonos/toxicidade , Larva/metabolismo , Neurotransmissores/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Tubulina (Proteína)/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Químicos da Água/toxicidade , Peixe-Zebra/metabolismoRESUMO
AIMS: Functional brain abnormalities, including altered cerebral perfusion and functional connectivities, have been illustrated in adults with attention-deficit/hyperactivity disorder (aADHD). The present study attempted to explore the alterations of cerebral blood flow (CBF) and resting-state functional connectivity (RSFC) simultaneously to understand the neural mechanisms for adults with ADHD comprehensively. METHODS: Resting-state arterial spin labeling (ASL) and blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) data were acquired for 69 male aADHD and 69 matched healthy controls (HCs). The altered CBFs associated with aADHD were explored based on both categorical (aADHD vs HCs) and dimensional (correlation with aADHD core symptoms) perspectives. Then, the seed-based RSFC analyses were developed for the regions showing significant alterations of CBF. RESULTS: Significantly decreased CBF in the large-scale resting-state networks regions (eg, ventral attentional network, somatomotor network, limbic network) and subcortical regions was indicated in aADHD compared with HCs. The correlation analyses indicated that the hypoperfusion in left putamen/global pallidum and left amygdala/hippocampus was correlated with ADHD inattentive and total symptoms, respectively. Further, weaker negative functional connectivity between left amygdala and bilateral supplementary motor area, bilateral superior frontal gyrus, and left medial frontal gyrus was found in adults with ADHD. CONCLUSION: The present findings suggested alterations of both cerebral perfusion and functional connectivity for the left amygdala in aADHD. The combination of CBF and RSFCs may help to interpret the neuropathogenesis of ADHD more comprehensively.
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Transtorno do Deficit de Atenção com Hiperatividade/fisiopatologia , Circulação Cerebrovascular , Vias Neurais/fisiopatologia , Adulto , Mapeamento Encefálico , Neuroimagem Funcional , Humanos , Imageamento por Ressonância Magnética , Masculino , Rede Nervosa/diagnóstico por imagem , Rede Nervosa/fisiopatologia , Vias Neurais/diagnóstico por imagem , Testes Neuropsicológicos , Oxigênio/sangue , Marcadores de Spin , Adulto JovemRESUMO
LncRNA TP73 antisense RNA 1T (TP73-AS1) plays an important role in human malignancies. However, the levels of TP73-AS1 and its functional mechanisms in pancreatic cancer metastasis remain unknown, and the clinical significance of TP73-AS1 in human pancreatic cancer is also unclear. In the present study, the levels of TP73-AS1 and its candidate target miR-141 in pancreatic cancer and adjacent normal tissue were detected using qRT-PCR. The association between TP73-AS1 levels and the clinicopathologic characteristics of pancreatic cancer patients were analyzed. The relationship between TP73-AS1 and miR-141, and miR-141 and its candidate target 3-hydroxybutyrate dehydrogenase type 2 (BDH2) was confirmed using dual-luciferase reporter assays. TP73-AS1 and/or miR-141 were knocked down using siRNA or an inhibitor in pancreatic cancer cells and cell migration and invasion then examined. The results showed that TP73-AS1 was up-regulated in pancreatic cancer tissue and cell lines. High levels of TP73-AS1 were correlated with poor clinicopathological characteristics and shorter overall survival. MiR-141 was a direct target for TP73-AS1, while BDH2 was a direct target for miR-141. The knockdown of TP73-AS1 significantly inhibited the migration and invasion of pancreatic cancer cells, while the miR-141 inhibitor significantly restored the migration and invasion. Therefore, TP73-AS1 positively regulated BDH2 expression by sponging miR-141. These findings suggest that TP73-AS1 serves as an oncogene and promotes the metastasis of pancreatic cancer. Moreover, TP73-AS1 could serve as a predictor and a potential drug biotarget for pancreatic cancer.
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Movimento Celular/genética , Regulação Neoplásica da Expressão Gênica , Hidroxibutirato Desidrogenase/genética , MicroRNAs/genética , Neoplasias Pancreáticas/genética , RNA Longo não Codificante/genética , Linhagem Celular Tumoral , Feminino , Humanos , Hidroxibutirato Desidrogenase/metabolismo , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica , Neoplasias Pancreáticas/metabolismo , Neoplasias Pancreáticas/patologia , Interferência de RNA , Regulação para CimaRESUMO
The exposure of a specific crystal face to a specific composition or a suitable carrier composition with synergistic effects can effectively improve the photocatalytic activity of the material and enhance its practical value. For choosing an ideal carrier, the primary factor is a large specific surface area. Herein, by using MIL-100(Fe) as the carrier, an egg-like TiO2/MIL-100(Fe) composite was successfully prepared, for the first time, via a facile two-pot hydrothermal method. XRD, SEM, TEM and other characterization methods showed that when the molar ratio of Ti : Fe was 0.3 : 1, the morphology of the TiO2/MIL-100(Fe) composite was completely egg-like. The TEM results showed that the {001} and {101} facets of TiO2 in the TiO2/MIL-100(Fe) composite were co-exposed. The BET results showed that the TiO2/MIL-100(Fe) composite had a large specific surface area and pore size. The larger pore size provided an effective channel for the photocatalytic degradation of MB and the interfacial effect of TiO2 and MIL-100(Fe). The separation efficiency of the photogenerated electron-hole pairs was effectively improved. The efficiency of 30% TiO2/MIL-100(Fe) in the photocatalytic degradation of MB reached 99.02% in 30 min under visible light. All these findings showed that the composite of the effectively charge-separated photocatalytic semiconductor and the porous MOF with a high specific surface area had a high potential application value for the photocatalytic degradation of organic pollutants.